Millions of women suffer from increased urinary urgency, frequency, incontinence, incomplete bladder emptying and irritative bladder conditions. There are two main types of incontinence, urge incontinence and stress incontinence, which have different physiological causes and different treatment options. Many women suffer from mixed incontinence, having both conditions.
Stress incontinence is largely the result of weakened ligaments, pelvic floor tissue and vaginal support, ultimately allowing the urethra to drop open in the setting of increased intraabdominal pressure. The process leading to stress incontinence is primarily mechanical and is associated with supportive tissue under the distal anterior vaginal wall. Strengthening the pelvic floor and supporting the urethra and/or bladder neck are safe and effective treatments for stress incontinence.
Urinary urgency, frequency, urge incontinence, incomplete bladder emptying, and nocturia represent a more complex process that is greatly neurologically mediated. Urinary urgency is marked by a strong, and often uncomfortable, urge to void that is difficult to suppress. Urge incontinence is defined by involuntary leakage of urine in the setting of urgency. The conditions noted above and other irritative bladder conditions may result from abnormal sensitivity of autonomic bladder nerves that prematurely communicate “fullness” to the central nervous system. These conditions may also result from erroneous nerve function in the central nervous system that allows the bladder to empty at inappropriate times. The underlying cause of these problems may be multifactorial. Ultimately, it is the autonomic nervous system that communicates bladder sensation, discomfort, or “fullness” and coordinates bladder filling and emptying.
Incomplete bladder emptying or urinary retention may result from inappropriate autonomic nerve signaling to the urethra and/or bladder. Some medical treatments are aimed at altering autonomic signal to the urethra, such that urethral tone is lessened. Others work by increasing bladder muscle tone by activating autonomic receptors in the bladder to cause a bladder contraction.
Many treatments of irritative bladder conditions are aimed at modifying nerve signaling between the bladder and the central nervous system. The goal is to affect both the afferent signals to the central nervous system that signal irritation, urgency, pressure or a sense of fullness and/or the efferent nerve signal that can trigger a rise in bladder pressure, cause discomfort, or leakage. Autonomic nerves transmit these signals. Treatment for urinary urgency, frequency, nocturia and urge incontinence is multifaceted, attempting to affect nerve signaling with behavioral, dietary, medical and physical therapies.
Urinary urge incontinence medications attempt to inhibit bladder contractions by disrupting signals between the autonomic nerves and the urinary tract. These drugs are not adequately effective for the majority of patients and also have significant systemic side effects that limit usage. Discontinuation rates at 6 months are well over 50% due to the high cost, lack of adequate effectiveness, and side effects. There are also contraindications to use, most of which are conditions affecting the elderly population that desires treatment for lower urinary tract symptoms.
An aggressive pelvic floor physical therapy regimen incorporating education, lifestyle, and dietary changes along with pelvic floor exercise training can be a reasonably effective treatment for urgency, frequency and urge incontinence in some patients. It is not clear how well exercise alone works to control urge related symptoms, as a large portion of the benefit gained from physical therapy is the result of education, cognitive-behavioral techniques, diet and lifestyle change. Patients are not often compliant beyond the short term, as the regimen can be costly, time consuming and difficult to comply with over time.
The goal of most pelvic floor exercises is to strengthen the muscles of the pelvic floor and increase nerve “tone.” These exercises activate the somatic nerves in order to cause pelvic floor muscle contraction. This is primarily a treatment for stress incontinence. A pelvic floor muscle contraction can secondarily affect autonomic nerves to the bladder via a spinal cord reflex arc. These exercises may dampen the signal to urinate or prevent leakage. They do not necessarily prevent the more common overactive bladder symptoms that occur before one has time to perform a contraction, such as a spontaneous sense of urgency or waking at night to void. It has been shown that urinary urgency alone, without leakage, is more bothersome to patients than urinary leakage alone. Effective treatment needs to prevent the spinal cord from perceiving inappropriate sensations in the first place.
Neuromodulation of autonomic nerves has become a useful treatment method for lower urinary tract symptoms, such as urgency, frequency, incontinence, incomplete bladder emptying, irritative symptoms, incomplete bladder emptying, fecal incontinence and related conditions. One technique involves an implanted stimulation lead over the S3 nerve root. It can be a successful treatment for patients who have failed other treatments.
Although use of the surgical implant over the S3 nerve root has been successful, the treatment has drawbacks. The main disadvantage is that the device requires surgical implantation of small electrical leads through a foramen in the sacrum and a stimulator device within the soft tissue above the gluteus maximus. Implantation typically requires two surgical procedures, exposure to radiation, and often requires additional surgery to revise or remove the components. It has also been reported that over 25% of patients will require surgical revision of either the implanted battery or lead to manage complications. Additionally, the current surgical implant often needs to be removed for some types of MRI. The device is also extremely expensive. In general, patients prefer less effective alternative therapies, as they often do not think bladder symptoms warrant surgery or they are not comfortable with the idea of a surgical implant.
Another drawback of the conventional surgical implant is that the stimulation occurs at the level of the nerve root, so somatic fibers traveling in the S3 nerve root are also stimulated before they branch off into somatic nerves. These nerves can cause the patients to feel vulvar, vaginal, anal and lower extremity muscle contractions or tingling. Still another limitation of the implantable stimulator is that the same one, or occasionally two, nerve roots are available and subject to all of the stimulation. As a result, the nerve becomes less responsive due to habituation rendering the lead less effective or ineffective. This phenomenon has been well established. Due to these many drawbacks, including risk of surgery, complications associated with the implant, cost, reduced effectiveness over time, and somatic symptoms associated with the implanted S3 sacral nerve modulator, this treatment has not been widely adopted despite its effectiveness.
The existing non-surgical electrical stimulation therapies include devices that are positioned in the vagina thereby avoiding some drawbacks of the surgical implant. However, these devices are often less effective and have their own drawbacks. Many conventional devices positioned in the vagina direct electrical impulses in the lower or distal vagina and/or adjacent to the pelvic floor. Electrical signals are sent through the vagina to paravaginal tissue, targeting nerves adjacent the pelvic floor muscles or the muscles themselves. The goal suggested by these conventional methods is generally to stimulate nerves adjacent the pelvic floor and to increase pelvic floor tension. Many of these therapies attempt to treat stress incontinence and/or simulate pelvic floor exercises. Yet, bladder filling, emptying and sensation are mediated by autonomic nerves, not somatic nerves. The inventor believes that these devices and therapies are often not as effective at treating urinary urgency, incontinence, nocturia, incomplete bladder emptying or other lower urinary tract symptoms as an implanted sacral nerve modulator because they do not sufficiently isolate stimulation to autonomic nerves.
A major limitation of these vaginal stimulation devices for treating most irritative urinary tract symptoms is that they indiscriminately send electrical impulses to both somatic and some distal autonomic nerve fibers adjacent to the lower and mid-vagina. They also often target somatic nerves, such as the pudendal nerve and its distal branches. The somatic nerves do not directly control bladder filling, emptying, or sensation. Activation of somatic nerves can cause increased pelvic floor tension, discomfort, and pain associated with pudendal nerve activation. Such conditions may actually contribute to urinary urgency, frequency and voiding dysfunction. Somatic nerves are quite sensitive, so the electrical impulses can be perceived even at low intensity, thereby limiting the full range of treatment protocols or precluding therapy altogether.
Thus, the inventor believes that the problem with present neuromodulation treatment methods is that they either require surgical implantation or, for vaginally inserted devices, the stimulation does not adequately target important autonomic nerve structures yet influences muscles and somatic nerves in the lower vagina providing less effective therapy for autonomically mediated urinary tract symptoms and contributing to undesirable side effects. Furthermore, the conventional implanted sacral nerve root therapies stimulate somatic nerves (although there are also autonomic—parasympathetic fibers near this location) and provide therapy to a very focal portion of a nerve, thereby contributing to habituation. These factors may provide less effective therapy for autonomically mediated urinary tract symptoms and contribute to undesirable side effects. Thus, optimal therapy would stimulate the autonomic nerves that mediate signal between the urinary tract and the central nervous system and/or end organ while avoiding activation of the pelvic floor and associated somatic nerves. Optimally, neuromodulation would be delivered directly to the autonomic nerves at the “gateway” between the urinary tract and the spinal cord while avoiding pelvic floor muscle and nerve activation.
The present invention is also directed to systems and methods for altering and improving (reducing) sympathetic tone. The autonomic nervous system maintains homeostasis and functional control of most organs in the body. The sympathetic arm of the system mediates the “fight or flight” response associated with a stress state, generally via norepinephrine, otherwise known as “adrenaline.” The sympathetic system is responsible for preparing animals for immediate action. The parasympathetic arm maintains organ function at rest. It is theorized that survival of early organisms was quite dependent on the ability to quickly adjust from rest (grazing) to extreme physical activity (fleeing a predator). This transition requires immediate coordination of many organs, glands and nerves that increase cardiac output, optimize respiratory function, increase skeletal muscle contractility, alter blood flow distribution, adjust visual depth perception, and trigger rapid-fire thinking. When the sympathetic tone is high, organs are operating at an extreme capacity, which is not healthy over time.
Outside of acute stress, organisms need to maintain a fine balance between the sympathetic and parasympathetic tone. In modern times humans are not often fleeing life-threatening danger. However, we tend to live in a chronic state of stress. Naturally, the sympathetic nervous output is upregulated in a chronic stress state. Chronic stress contributes to persistently elevated sympathetic tone, which has deleterious effects on most organs of the body. For example, the heart is very sensitive to even modest increases in circulating epinephrine. Chronic exposure to increased epinephrine levels results in a rise of blood pressure and heart rate that can contribute to many forms of heart disease, including arrhythmias, coronary artery disease, valvular dysfunction and heart failure. Alterations in cerebral blood flow resulting from stress, influenced by the sympathetic nervous system, can result in migraine headaches.
Metabolism is greatly affected by increased sympathetic tone, via increased release of cortisol. Cortisol is an adrenal hormone that alters metabolism of glucose, bone, muscle, adipose (fat) cells and connective tissue. Cortisol acts locally and systemically to mobilize metabolic resources for a stress response related action. Chronically elevated circulating cortisol levels can have serious and deleterious consequences including insulin resistance/diabetes, decreased bone formation (osteoporosis), inhibited collagen production (poor tissue quality and wound healing), decreased protein synthesis (atrophy), increased gastric acid secretion (ulcers and gastrointestinal bleeding), altered renal function (electrolyte imbalances), impaired hippocampal function (decreased learning ability and dampened memory retrieval), along with increased epinephrine sensitivity in blood vessels (hypertension). Cortisol also weakens the immune response by inhibiting T cell proliferation, which results in vulnerability to infection and cancer.
Stress and elevated sympathetic tone is also associated with increases in circulating inflammatory mediators, mainly Interleukin-6, which promote systemic inflammation. Inflammation is responsible for autoimmune conditions affecting nearly every organ in the body. Examples include dermatologic conditions (eczema), atherosclerosis (coronary artery disease and stroke), gastrointestinal (ulcerative coltis or Crohn's disease), lupus, arthritis, allergic reactions, pericarditis, myocytis, cataracts, pain conditions, interstitial cystitis, vasculitis, glomerulopathies, multiple sclerosis, iritis, asthma, and cancer. Pain is associated with inflammation and stress. Increased mortality has been associated with chronic exposure to increased stress and Interleukin-6 levels.
Many people simply maintain an elevated sympathetic tone, regardless of their stress level. Normal blood pressure and heart rate in healthy and relaxed people varies within a normal range, for example. Central obesity contributes to increased sympathetic output, regardless of stress level or cardiovascular health.
Ultimately, lowering sympathetic tone can improve specific disease states and overall health. Current approaches to decrease sympathetic tone include exercise, weight loss, relaxation techniques, meditation and cognitive behavioral therapies. These approaches are not always effective, achievable or sustainable.
The present invention is directed to improved systems and methods for stimulating nerves. The present invention is also specifically directed to systems and methods for altering sympathetic tone.